Glucocorticoids decrease interleukin-6 levels and induce mineralization ofcultured osteogenic cells from children with fibrous dysplasia

Fibrous dysplasia (FD) is a progressive hone disease in which abnormal fibr oblast proliferation results in the replacement of normal cancellous bone w ith an immature fibrous tissue that is poorly mineralized, The disease mani fests itself in the monostotic form in which only one bone is involved and the polyostotic form in which multiple bones at different sites are affecte d. The McCune-Albright syndrome is a variation of the polyostotic form in w hich patients demonstrate a greater extent of bone involvement and a variet y of endocrinopathies, Somatic activating mutations in the GNAS gene ha ce been demonstrated in the fibrotic lesions of patients affected with either monostotic or polyostotic FD. The increased cAMP levels caused by the G-pro tein mutations lead to increased interleukin-6 (IL-6) levels in the affecte d tissues, resulting in abnormal osteoblast differentiation and increased o steoclastic activity. Utilizing cell culture techniques that have been deve loped for mammalian bone marrow stromal cells, ne have successfully culture d osteogenic stem cells from the affected stroma of 11 FD patients, Cells c ultured from patients with polyostotic FD showed a high frequency of the G( s)alpha mutation, whereas cells from monostotic FD patients showed a lo tr frequency of the mutation. Both the normal and FD cells displayed the osteo genic phenotype when exposed to medium containing glucocorticoids, Glucocor ticoids also caused a dramatic inhibition of IL-6 mRNA and protein levels i n osteogenic cells cultured from the FD patients, These findings suggest th at chemical alteration of cellular function mag lend to new treatment optio ns for patients with FD.